10114229A novel phase 1 clinical trial for a next-generation oncolytic therapy targeting treatment of platinum-resistant high-grade serous ovarian cancerActiveCollaborative R&DInnovate UKAnnually 7,495 women in the UK are diagnosed with ovarian cancer (OC). \>75% of cases are diagnosed at an advanced stage (grade-III/IV) with poor long-term outcomes (<25% 5-year survival). Standard-of-care first-line treatments combine cytoreductive surgery, platinum-based chemotherapies, and paclitaxel. Although initially effective, most patients relapse and become resistant to platinum-based therapies. The are no effective treatments for platinum-resistant OC and patients have a life expectancy of less than 12-months. Whilst immunotherapies have shown great promise for many cancers, results for OC remain disappointing. This is believed to result from the heterogeneous and immune-suppressed nature of the tumour-microenvironment, and the high volume of cancer-associated-fibroblasts (CAFs), that create physical barriers to therapeutic- and immune-cell penetration, and promote tumour survival and proliferation mechanisms. Oncolytic viruses (OVs) are an emerging immunotherapy class that selectively infect cancer cells and induce immunogenic cell death, leading to tumour reduction, modulation of the tumour-microenvironment (lifting immune suppression), and stimulation of adaptive immune responses. Importantly, OVs demonstrate phenotypic selectivity, overcoming challenges of heterogeneity. However, existing OVs are primarily developed from seroprevelant wild-type viruses that are not evolved for oncolytic use, using simple cell-/animal-models that poorly model real tumour-/host-responses. Furthermore, OVs are unable to overcome CAF-associated extracellular barriers that hinder infection/spread. THEO-260 is a next-generation OV-therapeutic for the treatment of PROC, demonstrating world-first dual-efficacy (targeting both cancer- and CAF-cells), enabling effective treatment of stroma-rich tumours. IV-delivery enables THEO-260 to be incorporated seamlessly into standard-of-care practices. Step-advancements in features are achieved via Theolytic's revolutionary OV-platform. THEO-260 is anticipated to deliver a step-advancement in PROC treatment, significantly extending patient survival and quality-of-life.